Trifluoperazine reproduces in rat islets the effects of calcium omission on insulin secretion and de novo lipid synthesis, without affecting 45Ca2(+)-uptake.
Calmodulin is thought to mediate at least some of the effects produced by the elevation of cytosolic calcium in response to a B-cell secretagogue. Trifluoperazine, an inhibitor of calcium-calmodulin interaction, has been used to test, comparatively with calcium-omission, whether the changes of lipid metabolism accompanying the stimulation of insulin release by glucose and palmitate are dependent on activation by the calcium binding protein. Low doses of trifluoperazine (1 and 5 mumol/l) reproduced quantitatively and qualitatively the effects of calcium omission on both insulin secretion and de novo lipid synthesis, without altering islet 45Ca2(+)-uptake. The apparent dependence on calcium-calmodulin of the "de novo" synthesis of neutral lipids, but not of acidic phospholipids, might reflect a possible regulation of islet phosphatidate phosphohydrolase by calcium.
Vara
E
E
Departamento de Bioquímica, Facultad de Medicina, Madrid, Spain.
García
C
C
Tamarit-Rodríguez
J
J
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002132:Calcium Radioisotopes; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008055:Lipids / Q000096:biosynthesis*; D008297:Male; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014268:Trifluoperazine / Q000494:pharmacology*
D001786:Blood Glucose; D002132:Calcium Radioisotopes; D007328:Insulin; D008055:Lipids; D010169:Palmitic Acids; D014268:Trifluoperazine; D019308:Palmitic Acid; D005947:Glucose; D002118:Calcium